Sibling Pair Analysis Shows No Linkage of Generalized Osteoarthritis to the Loci Encoding Type Ii Collagen, Cartilage Link Protein or Cartilage Matrix Protein

Loughlin, John; Irven, Catherine; Fergusson, C. M.; Sykes, Bryan

doi:10.1093/rheumatology/33.12.1103

Cited by 61 publications

(31 citation statements)

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“…Because the COL2A1 gene product is abundantly present in cartilage, an important target tissue in osteoarthritis, sequence variation in this gene has been analyzed in relation to ROA. Although the gene has been implicated in ROA (30-32) controversy remains because other reports did not show evidence for COL2A1 as a candidate gene for osteoarthritis (33,34). Genetic mapping studies in pedigrees have demonstrated very close linkage between the COL2A1 and VDR loci (35) and the physical distance separating the two loci is Ͻ 740 kb (36).…”

Section: Discussionmentioning

confidence: 99%

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Uitterlinden¹,

Burger²,

Huang³

et al. 1997

J. Clin. Invest.

139

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Osteoporosis and osteoarthritis are age-related disorders of the skeleton with genetic components. Low bone density is a risk factor for osteoporotic fracture while osteoarthritis is associated with increased bone density. The 1,25-dihydroxyvitamin D 3 receptor (VDR) gene locus was previously found to be associated with bone density. We therefore studied the relationship between radiographic osteoarthritis at the knee and VDR genotype in a population-based sample ( n ϭ 846), using molecular haplotyping of anonymous intragenic DNA polymorphisms. Radiographic osteoarthritis was defined using the Kellgren score, which is based on the assessment of osteophytes and joint space narrowing (JSN). We show that one VDR haplotype allele is significantly overrepresented in individuals with knee osteoarthritis and associated with a 2.27-fold increased relative risk (95% confidence interval 1.46, 3.52). Adjustment for bone density at the femoral neck did not change these results, indicating that the association is not mediated by bone density. The association appeared to be largely explained by the presence of osteophytes rather than JSN. Our results indicate a role of the VDR gene in the pathogenesis of osteophytes while linkage disequilibrium with another nearby gene, i.e., the collagen type IIa1 gene encoding the most abundant protein in cartilage, might contribute to the association. ( J. Clin. Invest. 1997. 100:259-263.)

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Section: Discussionmentioning

confidence: 99%

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Uitterlinden¹,

Burger²,

Huang³

et al. 1997

J. Clin. Invest.

139

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“…Mutations in the type II collagen gene, COL2A1, have been observed in various types of chondrodysplasias. Studies performed in the early 1990s could not provide any evidence for an influence of COL2A1 variants in OA susceptibility (24). Analyses of COL2A1…”

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confidence: 92%

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

Valdes

Loughlin

Oene

et al. 2007

Arthritis & Rheumatism

180

118

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Objective. To assess whether the association of genetic polymorphisms with osteoarthritis (OA) in other populations could be replicated in a large, multicenter, mixed-sex, case-control study of clinical knee OA.Methods. Genetic polymorphisms in OA candidate genes were genotyped in 298 men and 305 women, ages 50-86 years, all of whom had a diagnosis of knee OA as assessed clinically and radiographically, and in 300 male and 299 female control subjects matched for age and ethnicity. Allele and haplotype frequencies for 5 genes (ASPN, CALM1, COL2A1, COMP, and FRZB) previously tested for association with hip and/or knee OA in other populations were compared between patients and control subjects, analyzing men and women separately.Results. The same FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype associated with hip OA in other populations of Caucasian women was shown to increase the risk of knee OA among the women (but not the men) in the current study (odds ratio [OR] 2.87, P < 0.04). The CALM1 SNP, which affects the risk of hip OA in Japanese individuals, was not shown to be associated with susceptibility to OA in men or women. COL2A1 haplotypes were demonstrated to be associated with a decreased risk of knee OA in men (OR 0.68, P < 0.005) but not in women. COMP haplotypes that were associated with susceptibility to knee OA were different in men and women (P < 0.014 and P < 0.032, respectively). A meta-analysis of these data and those from previously published reports indicated a strong association between the FRZB G324 allele (P < 0.0003) and suggested that an ASPN allele is protective against the risk of knee OA in Caucasians (P < 0.02).Conclusion. Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.

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“…general population [16,18]. Since then, the genetic influence on OA pathogenesis has consistently been shown by many epidemiological, twin-pair and family-clustering studies [18][19][20][21]. Genome-wide association and linkage-scan studies have uncovered a plethora of genes that may be implicated in OA aetiology [22], and now it is thought that the genetic influence could explain >50 % of the variations in susceptibility to this condition [16,18].…”

Section: Introductionmentioning

confidence: 99%

“…These include genes coding for structural proteins of the ECM, such as collagen type 2, and cytokines involved in the inflammatory process associated with this condition. Some genes discovered thus far do not pose a consistent increased susceptibility to OA development [18,20]. However, the involvement of the interleukin 1 (IL-1) gene and the asporin gene (ASPN) have been the most compelling, showing a significantly strong statistical association [22].…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis: genes, nature–nurture interaction and the role of leptin

Garner

Alshameeri

Khanduja

2013

International Orthopaedics (SICOT)

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Osteoarthritis (OA) is a common disease affecting patients at different ages regardless of gender or ethnicity. As with many chronic diseases, OA is thought to have a multifactorial aetiology, which is not fully understood. Whereas the pathophysiological process of OA can be analysed at a cellular and molecular level, the interaction between genes and lifestyle remains an important factor in the development of this disease. The expanding awareness of different genes that may play a role in OA, together with many chemical mediators thought to be associated with the progression of the disease, will help in better management of this condition. Some of the chemical mediators recently implicated in this condition are the adipokines (leptin, adiponectin and resistin). Few but consistent studies suggest that leptin in association with obesity could be an important factor in OA aetiology. Hence, this could establish a strong and direct molecular link between patient life style (nurture) and the pathological process of OA (nature). However, neither a clear mechanism nor a direct clinical association linking leptin to OA has yet been established. In this article, we explore some of the genetic and environmental factors in OA aetiology. We discuss leptin in obesity and assess its possible association with OA aetiology. This should emphasise the important role of health professionals in treating obesity in order to control OA symptoms and possibly progression.

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Sibling Pair Analysis Shows No Linkage of Generalized Osteoarthritis to the Loci Encoding Type Ii Collagen, Cartilage Link Protein or Cartilage Matrix Protein

Cited by 61 publications

References 0 publications

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Vitamin D receptor genotype is associated with radiographic osteoarthritis at the knee.

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

Osteoarthritis: genes, nature–nurture interaction and the role of leptin

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